Rhabdomyolysis in transplant patients

In a retrospective analysis of all our patients with seizure onset prior to age 16 years, 25 patients with primary generalized tonic (n = 10) or tonic-clonic (n = 15) seizures were identified. These patients constituted 5.7% of the total seizure patient population in our institute between the ages of 1 month and 16 years. The natural history of generalized tonic-clonic seizures is known to be benign; however, that of isolated primary generalized tonic seizures is not clear. Therefore, an attempt was made to characterize the patients suffering from primary generalized tonic seizures and determine their outcome. Analysis of our patient population shows that both seizure types are characterized by early onset of generalized seizures that appear in normally developed children with a normal electroencephalographic background. The children usually respond quickly to antiepileptic drugs. A long-term follow-up (mean period of 7.6 years) was possible in 84% of the patients, and showed that 95% of them were seizure free at the end of the follow-up period. There was no significant difference between the two groups in regard to age of onset, family history, and seizures at follow-up. In conclusion, the natural history of patients with generalized tonic seizures is similar to the benign course of those with generalized tonic-clonic seizures.     

Anti-viral effect of interferon-alpha on bovine viral diarrhea virus

PURPOSE: Lamotrigine (LTG) is recognised as effective add-on therapy for focal epilepsies, but this is the first double-blind, placebo-controlled, crossover study in treatment-resistant generalised epilepsy. METHODS: The study consisted of 2 x 8-week treatment periods followed by a 4-week washout period. Patients received doses of either 75 or 150 mg daily, depending on their concomitant antiepileptic drugs (AEDs). Long-term continuation was offered at the end of the study with open-label LTG. RESULTS: Five centres in Australia recruited 26 patients who were having absence, myoclonic, or generalized tonic-clonic seizures or a combination of these. Twenty-two patients completed the study. There was a significant reduction in frequency of both tonic-clonic and absence seizure types with LTG. A 350% decrease in seizures was observed for tonic-clonic seizures in 50% of cases and for absence seizures in 33% of evaluable cases. Rash was the only adverse effect causing discontinuation. Twenty-three of 26 opted for open-label LTG, with 20 still receiving LTG for a mean of 26 months. In these 20, 80% had > or =50% seizure reduction and five (25%) were seizure free. CONCLUSIONS: This study shows that LTG is effective add-on therapy in patients with refractory generalised epilepsies. Statistically significant reduction in seizures in both absence and tonic-clonic seizure types was seen even with low doses of LTG.     

Epilepsy and the heart

The relations between epilepsy and heart are complex and expressed in two opposite sides. (1) Cardiac arrhythmias may provoke epileptic seizures but these seizures are, in this case, syncopal attacks. Nevertheless, in the past, these clinical features have been individualized as "cardiac epilepsy" or epilepsy in cardiacs. However, true epileptic seizures could be observed in the course of a syncopal attack and a syncope may complicate the issue of an epileptic seizure. (2) On the other hand, epileptic seizures may provoke severe cardiac arrhythmias. The incidence rate of sudden death in patients with epilepsy is estimated to be 1/1000 patients. The exact neural mechanisms in cardiac arrhythmias seizures could explain only some of the sudden unexpected deaths observed in epileptic patients. The role of antiepileptic drugs on cardiac conduction as well as the effects of seizures or status epilepticus on the myocardium are other enigmatic aspects of the relations between epilepsy and heart.     

Fluorometric assessments of acrosomal integrity and viability in cryopreserved bovine spermatozoa

It is widely agreed that after two or more seizures patients should be given antiepileptic treatment, but there is still controversy about the treatment of patients after a first unprovoked seizure. In a multicenter, randomized, open trial, patients with a first tonic-clonic seizure were randomized to immediate treatment (carbamazepine, phenytoin, phenobarbital, or sodium valproate) or to treatment only after another seizure. Fifty-two (24%) of the 215 patients randomized to immediate treatment and 85 (42%) of the 204 randomized to delayed treatment experienced seizure recurrence during follow-up. Age, acute treatment of the seizure with benzodiazepines, remote etiologic factors, and EEG abnormalities were significant predictors of relapse. Of the immediately treated patients, 87% had no seizures for a year and 68% had no seizures for 2 years, whereas only slightly fewer initially untreated patients (83% and 60%) achieved these endpoints. Patients treated after the first seizure and those treated after seizure relapse had the same time-dependent probability of achieving 1 and 2 seizure-free years. None of the variables that were prognostic predictors of relapse was significantly associated with the probability of having 1 or 2 years of seizure control. Anticonvulsants in patients presenting a first tonic-clonic seizure reduce the risk of relapse; however, 50% of patients who are not treated will never experience a second seizure. Moreover, the probability of long-term remission is not influenced by treatment of the first seizure.     

Ofloxacin-induced seizure

OBJECTIVE: To describe a possible case of ofloxacin-induced generalized tonic-clonic seizure. Although the etiology is unknown, ofloxacin most likely precipitated this patient's seizure threshold because of sepsis or secondary to drug accumulation due to the patient's compromised renal function. CASE SUMMARY: A 69-year-old white woman with non-small-cell lung cancer and a history of central nervous system metastatic disease treated with radiation therapy presented to the emergency department with symptoms of urosepsis. Because of multiple drug allergies she was started on ofloxacin (hospital formulary quinolone). After 4 days of therapy she developed a generalized tonic-clonic seizure. A computed tomography scan of the head with and without contrast was negative. The ofloxacin was discontinued and aztreonam therapy was started. Phenytoin therapy was instituted and, despite serum concentrations below the conventional therapeutic range, there was no recurrence of seizure. Subsequent discontinuation of phenytoin did not result in a seizure for this patient. DISCUSSION: Seizures induced by the fluoroquinolones are uncommon. The histopathologic features of this phenomenon are currently unknown. In this patient, imaging studies were negative for structural defects, ruling out metastasis as the cause of the seizure. Therefore, an investigation of drug-related causes ensued. The most likely offending agent was ofloxacin. Ofloxacin has been reported in the literature as a cause of seizures in patients with compromised renal function. CONCLUSIONS: This case and other reports indicate that fluoroquinolones, including ofloxacin, may contribute to seizure development in patients with or without a history of epilepsy. Fluoroquinolone therapy should be used with caution in patients with risk factors for the development of drug-induced seizures.     

Prenatal morphine exposure induces age-related changes in seizure susceptibility in male rats

The purpose of this study was to investigate the effects of prenatal exposure to morphine (5-10 mg/kg on days 11-18 of gestation) on flurothyl seizure susceptibility in adult and developing male rats. In adult rats, prenatal morphine exposure increased the threshold to clonic seizures but not to tonic-clonic seizures. The effects of prenatal morphine exposure on clonic seizures were age dependent. At postnatal day (PND) 15, prenatal drug exposure did not alter the seizure threshold. At PND 25, there was a reduction in the threshold but by PND 38, the clonic seizure threshold was increased and this increase persisted into adulthood. Prenatal exposure to morphine did not alter the tonic-clonic seizure threshold in any age group of intact male rats. A group of male rats prenatally exposed to morphine was gonadectomized in adulthood. In gonadectomized rats both clonic and tonic-clonic thresholds were increased. These results suggest that exposure to morphine during mid to late gestation induces age-dependent alterations in the susceptibility to clonic but not tonic-clonic seizures. In adult male rats the threshold to tonic-clonic seizures is influenced by prior gonadectomy in adulthood.     

The choleretic effects of licorice: identification and determination of the pharmacologically active components of Glycyrrhiza glabra

The authors retrospectively reviewed ten pediatric brain tumor patients with intractable seizures who underwent lesionectomy without intentional identification and resection of the epileptogenic region to assess the clinical features and seizure outcome after lesionectomy in such patients. Seizures were complex partial in seven cases and simple partial, absence, and generalized tonic-clonic in one case each. Tumors were located at the medial temporal lobe in four cases, at the frontal lobe in four cases, at the parietooccipital and the suprasellar areas in one case each. The most common pathology was benign oligodendroglioma (five cases) followed by ganglioglioma (two cases). Others were pleomorphic xanthoastrocytoma, hamartoma, and primitive neuroectodermal tumor (one case each). In four cases, complete removal of the tumor was feasible. Postoperatively nine of the ten patients showed favorable seizure control (Engel's classification 1 and 2) and of these, six were seizure-free during the follow-up period (mean duration: 40 months). Therefore, lesionectomy can be an appropriate initial treatment for patients with brain tumor and medically intractable seizures.     

Vigabatrin and lamotrigin: experiences with 2 new anticonvulsants in the Swiss epilepsy clinic

Vigabatrin and lamotrigine are two new antiepileptic drugs which have recently become available. Vigabatrin is a specific and irreversible inhibitor of the enzyme gamma-amino-butyric-acid (GABA) transferase. Its administration leads to a long lasting increase in GABA, the most important inhibitory neurotransmitter. Vigabatrin is effective in both adults and children in the treatment of partial and especially complex-partial seizures. After add-on in vigabatrin to their therapeutic drug regime in 116 of our own patients, 39% of previously therapy resistant patients reported a reduced seizure frequency of at least 50% and 6% of them became seizure free. In secondarily generalized epilepsies the best results were observed in axial (infantile) spasms. In addition there was some improvement in tonic and convulsive seizures. Single patients showed increased myoclonic and clonic seizures. Initial efficacy was not always maintained during follow-up. In the experience of other authors, vigabatrin is also effective in the treatment of infantile spasms. It is not suitable for the treatment of generalized epilepsies with absences and myoclonic seizures. Most patients tolerate vigabatrin very well, although psychotic episodes are sometimes reported. So far there have been no relevant hepatic or hematological side effects. Lamotrigine is also effective in the treatment of partial seizures, for which it is approved. However, uncontrolled studies and our own experience have shown that it is even more effective in generalized seizures. As add-on therapy in absences and tonic or tonic-clonic seizures, a significant reduction in seizure frequency--in individual cases seizure freedom--can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dynorphin and epilepsy

Studies on dynorphin involvement in epilepsy are summarised in this review. Electrophysiological, biochemical and pharmacological data support the hypothesis that dynorphin is implicated in specific types of seizures. There is clear evidence that this is true for complex partial (limbic) seizures, i.e. those characteristic of temporal lobe epilepsy, because; (1) dynorphin is highly expressed in various parts of the limbic system, and particularly in the granule cells of the hippocampus; (2) dynorphin appears to be released in the hippocampus (and in other brain areas) during complex partial seizures; (3) released dynorphin inhibits excitatory neurotransmission at multiple synapses in the hippocampus via activation of kappa opioid receptors; (4) kappa opioid receptor agonists are highly effective against limbic seizures. Data on generalised tonic-clonic seizures are less straightforward. Dynorphin release appears to occur after ECS seizures and kappa agonists exert a clear anticonvulsant effect in this model. However, more uncertain biochemical data and lack of efficacy of kappa agonists in other generalised tonic-clonic seizure models argue that the involvement of dynorphin in this seizure type may not be paramount. Finally, an involvement of dynorphin in generalised absence seizures appears unlikely on the basis of available data. This may not be surprising, given the presumed origin of absence seizures in alterations of the thalamo-cortical circuit and the low representation of dynorphin in the thalamus. In conclusion, it may be suggested that dynorphin plays a role as an endogenous anticonvulsant in complex partial seizures and in some cases of tonic-clonic seizures, but most likely not in generalised absence. This pattern of effects may coincide with the antiseizure spectrum of selective kappa agonists.     

Ectopic cerebral tissue in the middle ear. A case report

Most idiopathic generalized epilepsies have an onset in childhood or adolescence, with a moderate second incidence peak in the presenium predominantly in women. This study addressed the question of a later onset. The available literature and the records of four personal data sets (two prospective incidence surveys of epileptic seizures, one prevalence study of epilepsy, and one clinical series of individuals with epilepsy) were screened for patients who had experienced a first generalized convulsive seizure with bilateral spike-wave complexes on EEG after 60 years of age. Reports of first idiopathic generalized tonic-clonic seizures occurring after age 60 were extremely rare and none was found in our four cohorts regardless of the methodology involved. Only five case reports were found, all involving a woman. Two had a family history of seizure disorders and two had had at least one seizure earlier in life. Idiopathic generalized epilepsy of late onset, if this condition actually exists, is likely to be the consequence of a genetic predisposition triggered by acquired epileptogenic factors.     

Losing consciousness: role of the venous lactate levels in the diagnosis of convulsive crises

OBJECTIVES: This prospective study was conducted to evaluate the usefulness of venous lactate assay in the diagnosis of generalized seizures. PATIENTS AND METHODS: Over a three month period, 78 consecutive adults admitted to the emergency unit for unconsciousness were included in the study. Three study groups were defined: patients with generalized seizures (n = 22), unconscious patients without seizure (n = 34) and known epileptic patients with unexplained malaises (n = 22). Patients with a disease susceptible of increasing lactate levels were excluded. Peripheral venous blood was drawn to determine lactates, bicarbonates and pH on a blood gas analyzer. All determinations were performed within 5 minutes of blood withdrawal. CPK level was also determined with an enzymatic method. RESULTS: In patients who had seizures, venous lactate levels were higher than those in patients who had no seizures: 4.3 +/- 0.5 mmol/l in generalized seizure patients versus 1.64 +/- 0.1 and 2.2 +/- 1.39 in unconscious patients without seizure and known epileptic patients with unexplained malaise respectively. The threshold lactate level of 2.5 mmol/l given by ROC curves gave a 0.97 specificity and a 0.73 sensitivity. DISCUSSION: The acidosis observed in patients with generalized seizures results from the combined effects of respiratory and metabolic acidosis. High lactate level would be a consequence of hypoxemia, per seizure rise in catecholamines, and aerobic and anaerobic metabolism in muscles during the tonic-clonic phase. In patients presenting in an unconscious state, increased lactate levels, even when determined up to 2 hours after venous blood withdrawal, could be a useful parameter for the diagnosis of epileptic seizure.     

Echocardiographic findings, 24-hour electrocardiographic Holter monitoring in patients with rheumatoid arthritis according to Steinbrocker''s criteria, functional index, value of Waaler-Rose titre and duration of disease

This study aims to understand seizure control outcomes and the risk of developing new wake seizures (WS) related to the different types of pure sleep epilepsies (SE), which is important in making rational management plans. A retrospective review of the Yonsei Epilepsy Clinic Registry identified 63 patients with pure SE not belonging to any specific epileptic syndromes. They were divided into the group of generalized tonic-clonic seizures during sleep (S-GTCS : n = 21) and the group of partial epilepsies during sleep (S-PE: n = 42) on the basis of seizure phenomenology, EEG, and neuroimaging data. These patients were followed for 2 years and their clinical variables were analysed for seizure control outcomes and development of new WS. Of 21 patients with S-GTCS, 17 achieved a seizure-free outcome and only one patient developed a new WS, which was consistent with a partial-onset secondary GTCS in phenomenology. Of 42 patients with S-PE only 15 patients achieved a seizure-free outcome and 11 patients developed WS during the 2-year follow-up period. Higher baseline seizure frequency and longer duration of epilepsy were associated with a higher incidence of new WS. The results suggest that the patients with S-GTCS carry a favorable clinical course, thus driving privileges or freedom of daily activities can be conferred without delay once their seizures are well controlled. However, the seizure control outcome was poor and the development of WS was frequent in patients with recurrent S-PE.     

Efficacy of topiramate

In controlled clinical trials, topiramate (Topamax) has demonstrated efficacy in refractory patients with complex partial seizures and secondarily generalized tonic-clonic seizures. Approximately 45 percent of 534 patients had a > or = 50 percent reduction in seizure frequency. Limited open label trials have shown that topiramate has broad spectrum activity and may be effective in patients with primary generalized epilepsies. The efficacy of topiramate compares very favourably with the efficacy of other new antiepileptic drugs recently introduced.     

Magnesium sulfate versus phenytoin for seizure prevention in amygdala-kindled rats

OBJECTIVE: Magnesium sulfate is widely used for seizure prophylaxis in preeclampsia-eclampsia. However, its anticonvulsant effects in other types of seizures have not been proved. Diphenylhydantoin has been widely characterized as the "gold standard" of anticonvulsants. In this study we compared the anticonvulsant effects of therapeutic blood levels of magnesium sulfate and phenytoin in seizures generated in amygdala-kindled rats. STUDY DESIGN: Eighteen male rats had a bipolar electrode stereotaxically implanted into the central nucleus of the amygdala. After recovery an electrical seizure threshold was determined for each rat. Rats were stimulated twice daily at their seizure thresholds (i.e., kindling) until three consecutive generalized tonic-clonic seizures occurred. Kindled rats randomly received one of the following intravenous injections in a volume of 1.5 ml/kg: saline solution, magnesium sulfate (30, 60, or 90 mg/kg), or phenytoin (12.5, 25, or 50 mg/kg). Fifteen minutes after injection rats were stimulated at their seizure thresholds, and electrical and behavioral seizure activity was assessed. Statistical comparisons were made by analysis of variance and post hoc comparisons when appropriate. RESULTS: Magnesium sulfate had no effect on any of the seizure parameters assessed. Phenytoin significantly reduced seizure duration (p < 0.01), duration of postictal depression (p < 0.01), and behavioral seizure stage (p < 0.01). CONCLUSION: Amygdala-kindled seizures are more potently inhibited by phenytoin than by magnesium sulfate.     

The long-term course of spike and wave complexes in the waking EEG of chronic schizophrenics

Nineteen chronic schizophrenics (8 males and 11 females) showed at least one spike and wave complex (SpW) in their rested-awake EEGs during long-term neuroleptic treatment. The age at the first appearance of the SpW ranged from 16 to 60 years, and the duration of neuroleptic medication preceding its appearance was from 1 to 35 years. Two types of SpW waveform were discriminated; one was a diffuse high voltage isolated 3.5-4 Hz SpW complex, and the other a diffuse moderate voltage 5-6 Hz SpW burst. In EEG studies repeated over the long-term, the presence of SpW was transient in 11 cases, intermittent in 5 cases, and continuous in 3 cases. Three patients had generalized tonic-clonic clinical seizures; two of their EEGs did not show SpW until after the onset of seizures. All three responded well to adjunctive anticonvulsant therapy. The other 16 patients exhibited SpW but did not have clinical seizures with or without prophylactic use of anticonvulsants. The SpW in the EEG of chronic schizophrenics might be an indicator of predisposition for seizure, but it is not a good predictor of seizure.     

Ictal oroalimentary automatisms with preserved consciousness: implications for the pathophysiology of automatisms and relevance to the international classification of seizures

A patient showing seizures presenting ictal automatisms with preserved consciousness is reported. A 30-year-old, right-handed man with normal development and without family history of epilepsy was referred for surgical treatment of epilepsy. At 15 he began to have seizures, starting with an epigastric aura, occasionally developing automatisms (lip-smacking, chewing), sometimes followed by tonic-clonic convulsions. At the time of referral, he averaged six convulsive seizures per year and one nonconvulsive per week. His sleep EEG showed sharpened slow activity over the right anterior quadrant magnetic resonance imaging (MRI) showed a benign lesion in the mesial aspect of the right occipital lobe. Simultaneous video monitoring and intracranial EEG with subdural strips recording from the right temporal and occipital lobes was undertaken. During one seizure, he had pronounced oroalimentary automatisms while holding a conversation with a technician, answering her questions, and explaining details of his seizures. Memory of this event was preserved. At seizure onset, spike activity was seen at the mesial occipital strips. At midseizure, high-voltage sharpened delta was seen throughout the right hemisphere. Left-sided scalp electrodes remained relatively uninvolved. The lesion, a dysembryoplastic neuroepithelial tumour was removed. Surgery was followed by abolition of seizures described. Because it is agreed that complex partial seizures require impaired consciousness, a history of automatisms with retained consciousness usually suggests nonepileptic attacks. This case suggests that automatisms in epileptic seizures can take place with minimal loss of consciousness, particularly if there is widespread but unilateral involvement. The need for a revision of the International Classification is suggested.     

Semiological seizure classification

We propose an epileptic seizure classification based exclusively on ictal semiology. In this semiological seizure classification (SSC), seizures are classified as follows: a. Auras are ictal manifestations having sensory, psychosensory, and experiential symptoms. b. Autonomic seizures are seizures in which the main ictal manifestations are objectively documented autonomic alterations. c. "Dialeptic" seizures have as their main ictal manifestations an alteration of consciousness that is independent of ictal EEG manifestations. The new term "dialeptic" seizure has been coined to differentiate this concept from absence seizures (dialeptic seizures with a generalized ictal EEG) and complex partial seizures (dialeptic seizures with a focal ictal EEG). d. Motor seizures are characterized mainly by motor symptoms and are subclassified as simple or complex. Simple motor seizures are characterized by simple, unnatural movements that can be elicited by electrical stimulation of the primary and supplementary motor area (myoclonic, tonic, clonic and tonic-clonic, versive). Complex motor seizures are characterized by complex motor movements that resemble natural movements but that occur in an inappropriate setting ("automatisms"). e. Special seizures include seizures characterized by "negative" features (atonic, astatic, hypomotor, akinetic, and aphasic seizures). The SSC identifies in detail the somatotopic distribution of the ictal semiology as well as the seizure evolution. The advantages of a pure SSC, as opposed to the current classification of the International League Against Epilepsy (ILAE), which is actually a classification of electroclinical syndromes, are discussed.     

Müllerianosis of the urinary bladder: clinical and immunohistochemical findings

BACKGROUND: Intranasal desmopressin has been used extensively to treat primary nocturnal enuresis. While it has proven to be a safe, effective agent for many who are affected by this condition, the potential for complications exists. OBJECTIVES: To report a case of severe hyponatremia associated with a generalized tonic-clonic seizure in a 10-year-old boy who had been receiving intranasal desmopressin nightly for nocturnal enuresis and to briefly review therapeutic options for nocturnal enuresis; and to present the role of desmopressin. SETTING: Georgetown University Medical Center, Washington, DC. INTERVENTION: Fluid restriction and intravenous isotonic saline solution with 5% dextrose was administered to raise the serum sodium level. OUTCOME: Prevention of further seizures with normalization of serum sodium levels without any obvious neurological sequelae. CONCLUSIONS: This case illustrates the importance of weighing the benefits and risks of intranasal desmopressin therapy.     

Modeling and measurement of the spontaneous mutation rate in mammalian cells

In order to examine the respiratory effects of tonic-clonic seizures and their treatment with i.v. diazepam or lorazepam, we utilized a spontaneously breathing piglet seizure model. A tracheostomy, arterial catheter, and epidural electrodes were inserted and pigs were maintained under ketamine anesthesia. After baseline recordings, seizures were induced with a pentylenetetrazol (PTZ) bolus and a 20 min infusion (5-6 mg/kg/min). After 10 min of PTZ infusion, randomly assigned animals received diazepam (D; N = 7; 0.5 mg/kg), lorazepam (L; N = 7; 0.2 mg/kg), or 0.9% saline (C; N = 7; controls) by rapid peripheral vein injection. Minute ventilation (Ve), Pa(CO2), and the pressure change in response to airway occlusion at end-expiration (P0.1) were measured at standard intervals. All groups had comparable increases in respiratory drive during untreated seizures. Changes in Ve and P0.1 were reduced to at or below baseline values in groups D and L, but not C, from 2 to 45 min after treatment (P < 0.05). No significant changes were observed in Pa(CO2) after either intervention. Following anticonvulsants, the cumulative duration of seizures was significantly reduced in L and D groups, compared to C (P < 0.05). We conclude that increases in respiratory drive occur during tonic-clonic seizures induced with PTZ. Amelioration of seizure activity with lorazepam or diazepam results in a reduction in respiratory drive, but not respiratory failure, in this tracheostomized model.     

Cryosurgery for hemangiomas

Children with the long QT syndrome (LQTS) are prone to life threatening ventricular arrhythmias. These arrhythmias may result in syncope and seizures that are often attributed incorrectly to a seizure disorder or to common fainting. The untreated mortality for symptomatic children with the LQTS is high but is improved significantly with therapy. Paediatricians should be aware of the presentations of the syndrome. Recommendations for screening for the syndrome are given.